“Pembrolizumab monotherapy has shown antitumor activity and a manageable safety profile in patients with metastatic TNBC,” said Javier Cortés, MD, PhD, of the Vall d’Hebron Institute of Oncology, in Barcelona, who presented results of the KEYNOTE-355 trial. “The immunomodulatory properties of chemotherapy suggest that combining pembrolizumab with chemotherapy might enhance antitumor activity.”
The new study included 847 patients randomly assigned to receive either pembrolizumab plus chemotherapy (investigator’s choice of nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin; 566 patients) or placebo plus chemotherapy (281 patients).
The median age in both the pembrolizumab and placebo groups was 53 years. In both groups, 75.1% of patients had a PD-L1 combined positive score (CPS) ≥ 1. In the pembrolizumab group, 38.9% of patients had a CPS ≥ 10, compared with 36.7% in the placebo group. Chemotherapy was relatively evenly split between taxanes and the gemcitabine/carboplatin combination.
Among patients with a PD-L1 CPS ≥ 10, the median PFS was 9.7 months with pembrolizumab and 5.6 months with chemotherapy alone (HR 0.65, 95% CI [0.49, 0.86]; p = 0.0012). At 6 months, the PFS rate with pembrolizumab was 65.0%, compared with 46.9% without it. At 12 months, those rates were 39.1% and 23.0%, respectively.
Pembrolizumab was also better in the group with CPS ≥ 1, although this result did not meet the prespecified requirements for statistical significance. The median PFS in these patients was 7.6 months with pembrolizumab and 5.6 months without (HR 0.74, 95% CI [0.61, 0.90]; p = 0.0014, not meeting prespecified value of p = 0.00111). At 6 months, the groups had PFS rates of 56.4% and 46.6%, respectively; at 12 months, PFS was 31.7% and 19.4%, respectively.
In the intention-to-treat analysis of the full cohort, regardless of PD-L1 status, the median PFS was 7.5 months with pembrolizumab and 5.6 months with placebo (HR 0.82, 95% CI [0.69, 0.97]). The 6-month PFS rates were 55.4% and 47.8%, respectively, and the 12-month PFS rates were 29.8% and 20.9%, respectively.
Among patients with a PD-L1 CPS ≥ 10, the PFS benefit with pembrolizumab was preserved across most subgroups. The one exception was in patients with a prior disease-free interval of less than 12 months, although Dr. Cortés noted the small number of patients in this group (66 in total).
The rate of treatment-related adverse events (TRAEs) was similar between the groups, with 96.3% of patients experiencing any-grade TRAEs in the pembrolizumab group and 95.0% in the placebo group. Grades 3 to 5 TRAEs occurred in 68.1% and 66.9% of patients, respectively; events leading to discontinuation of any drug occurred in 18.1% of patients in the pembrolizumab group and in 11.0% in the chemotherapy-alone group.
“These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic TNBC,” Dr. Cortés concluded.
Catherine M. Kelly, FRCPI, of Mater Misericordiae University Hospital, in Dublin, was the discussant for the study. She said that the lack of benefit seen in patients with CPS < 1 is consistent with the previously reported IMpassion130 trial, but not with KEYNOTE-522, suggesting the importance of higher PD-L1 expression, specifically, in the metastatic setting [2,3].
Dr. Kelly noted several remaining questions, including whether the specific chemotherapy partner matters, and whether those patients with PD-L1 CPS between 1 and 10 do derive benefit from the combination.
“Overall survival results are eagerly awaited, and needed, to fully establish the clinical utility of this combination,” Dr. Kelly said.
- Cortes J, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 1000.
- Schmid P, et al. N Engl J Med. 2018;379(22):2108‐2121.
- Schmid P, et al. N Engl J Med. 2020;382(9):810‐821.
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Table of Contents: ASCO 2020
Featured articles
COVID-19 & Telemedicine
COVID-19 and Cancer Consortium Registry: initial results
Oncology hospital-at-home model reduces hospitalizations, emergency department visits, and costs
Nurse-led telephone triage system reduces hospitalizations, helps patients manage symptoms at home
Melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Pembrolizumab plus low-dose ipilimumab well tolerated after progression on PD1 antibody therapy
Toripalimab plus axitinib effective in metastatic mucosal melanoma
Breast & Ovarian Cancer
Advanced breast cancer: locoregional therapy does not improve OS
T-DM1 does not improve safety or efficacy in HER-2 positive early breast cancer; favorable iDFS reported
Maintenance olaparib improves OS in relapsed ovarian cancer with BRCA1/2 mutation
Combination pembrolizumab/chemo improves PFS in metastatic TNBC
Effect of veliparib with or without cisplatin in breast cancer: results of SWOG S1416
PHOEBE, a phase 3 trial comparing pyrotinib and lapatinib in HER2-positive metastatic breast cancer
BYLieve demonstrates efficacy of PIK3CA-directed treatment post CDK4/6-ihibition
Strategies emerge for chemotherapy de-escalation in HER2-positive breast cancer
Multiple Myeloma
Carfilzomib: no PFS benefit for multiple myeloma
Lung Cancer
ES-SCLC: tremelimumab + durvalumab + chemotherapy misses endpoint
Adjuvant osimertinib in NSCLC: practice changing ADAURA trial
ES-SCLC: pembrolizumab KEYNOTE-604 data
Second-line gemcitabine plus ramucirumab significantly improves overall survival
Tiragolumab and atezolizumab: ORR in NSCLC
MET-amplified advanced NSCLC responds well to MET inhibitor capmatinib
Genitourinary Cancer
Urothelial cancer: avelumab works as maintenance therapy
ARAMIS final OS and nmCRPC safety outcomes
Final survival results from phase 3 SPARTAN trial
Novel drug for kidney cancers/VHL patients
Primary analysis from IMvigor010, adjuvant atezolizumab in high risk muscle-invasive urothelial carcinoma
First randomised trial of Lu-PSMA in mCRPC progressing after docetaxel
Gastrointestinal Cancer
HER2-expressing metastatic colorectal cancer: trastuzumab deruxtecan
REGOMUNE: a phase 2 study combining regorafenib and avelumab
Cardiotoxicity: consider switching to S-1
Perioperative chemotherapy for resectable pancreatic ductal adenocarcinoma
Real-world data of sequential sorafenib followed by regorafenib in unresectable HCC
Paediatric Cancer
Sustained improvements in quality of life with larotrectinib
Promising first immunotherapy trial in placental trophoblastic tumours
Precision medicine for poor-prognosis paediatric patients
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